Maintenance of tolerance and restoration of host homeostasis following insults relies on a complex and coordinated set of innate and adaptive responses. These tissue tailored responses are controlled by specialized populations of cells that integrate local cues such as defined metabolites or cytokines in order to induce responses in a way that preserve the functional requirements of each tissue. Our work helped to identify some of these tissue specific factors and immunological networks and their role in the development of appropriate and controlled immune responses. Notably our work identified mechanisms by which the host acquires tolerance to food or commensal antigen and how inflammation disrupts these regulatory pathways. Our current work explores novel mechanisms of regulation by tissue resident and inflammatory cells and identifies key factors controlling the function and survival of regulatory and effector cell populations at barrier sites.